A retrospective regulatory analysis of FDA recalls carried out by pharmaceutical companies from 2012 to 2023.

To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or violates FDA regulations. This study investigates the types, causes and consequences of recalls, as well as FDA participation and suitable recall strategies. We relied on the FDA website to gather recall data sets from 2012 to 2023, collecting information on the date of issuance, company and type of violation. The most frequent causes for recalls were sterility issues and inadequate compliance with current good manufacturing practices (cGMP). An examination of sterility recalls revealed two primary causes: a lack of assurance in sterility (accounting for 48% of recalls) and instances of non-sterility (making up 45% of recalls). A thorough examination of cGMP recalls revealed five primary types of violations: process control issues, inadequate storage practices, manufacturing problems, the presence of nitroso-amine impurities and concerns regarding stability. The findings demonstrate that sterility and cGMP compliance are FDA priorities. Pharmaceutical companies must, therefore, enhance quality compliance and create effective quality management systems that oversee the manufacturing process, quality control, personnel training and documentation to avoid these recalls. Companies should establish an internal compliance checklist and be prepared for the rectification process.

Multifaceted therapeutic applications of biomimetic nanovaccines.

The development of vaccines has had a crucial role in preventing and controlling infectious diseases on a global scale. Innovative formulations of biomimetic vaccines inspired by natural defense mechanisms combine long-term antigen stability, immunogenicity, and targeted delivery with sustained release. Types of biomimetic nanoparticle (NP) include bacterial outer membrane vesicles (OMVs), cell membrane-decorated NPs, liposomes, and exosomes. These approaches have shown potential for cancer immunotherapy, and in antibacterial and antiviral applications. Despite current challenges, nanovaccines have immense potential to transform disease prevention and treatment, promising therapeutic approaches for the future. In this review, we highlight recent advances in biomimetic vaccine design, mechanisms of action, and clinical applications, emphasizing their role in personalized medicine, targeted drug delivery, and immunomodulation.

Advanced drug delivery and therapeutic strategies for tuberculosis treatment.

Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance.

Lyotropic liquid crystalline phases: Drug delivery and biomedical applications.

Liquid crystal (LC)-based nanoformulations may efficiently deliver drugs and therapeutics to targeted biological sites. Lyotropic liquid crystalline phases (LLCPs) have received much interest in recent years due to their unique structural characteristics of both isotropic liquids and crystalline solids. These LLCPs can be utilized as promising drug delivery systems to deliver drugs, proteins, peptides and vaccines because of their improved drug loading, stabilization, and controlled drug release. The effects of molecule shape, microsegregation, and chirality are very important in the formation of liquid crystalline phases (LCPs). Homogenization of self-assembled amphiphilic lipids, water and stabilizers produces LLCPs with different types of mesophases, bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes). Moreover, many studies have also shown higher bioadhesivity and biocompatibility of LCs due to their structural resemblance to biological membranes, thus making them more efficient for targeted drug delivery. In this review, an outline of the engineering aspects of LLCPs and polymer-based LLCPs is summarized. Moreover, it covers parenteral, oral, transdermal delivery and medical imaging of LC in targeting various tissues and is discussed with a scope to design more efficient next-generation novel nanosystems. In addition, a detailed overview of advanced liquid crystal-based drug delivery for vaccines and biomedical applications is reviewed.

Nanosuspension encapsulated chitosan-pectin microbeads as a novel delivery platform for enhancing oral bioavailability.

The current study aimed to overcome the poor solubility and colon-specific delivery of curcumin (CUR) by formulating a curcumin nanosuspension (CUR-NS) using the antisolvent precipitation method. Freeze-dried CUR-NS was encapsulated into microbeads (CUR-NS-MB) by the ionotropic gelation method using zinc chloride (as a cross-linking agent) with the help of rate-controlling polymers, pectin, and chitosan. Furthermore, cellulose acetate phthalate (CAP) is incorporated as an enteric polymer to protect against acidic medium degradation. Particle size, surface morphology, interaction studies, and entrapment studies were performed to optimize CUR-NSs. Nanosuspensions stabilized with hydroxypropyl methylcellulose (HPMC E-15; 1 % w/v) showed an average particle size of 193.5 ± 4.31 nm and a polydispersity index (PDI) of 0.261 ± 0.020. The optimized microbeads (CUR-NS-MB) showed 89.45 ± 3.11 % entrapment efficiency with a drug loading of 14.54 ± 1.02 %. The optimized formulation (CUR-NS-MB) showed colon-specific in vitro drug release bypassing acid pH degradation. In animal studies, a 2.5-fold increase in Cmax and a 4.4-fold increase in AUC048h were observed with CUR-NS-MB, which was more significant than that of plain CUR. Therefore, the developed CUR-NS-MB has the potential to be used as a colon-specific delivery system.

Advanced pulmonary drug delivery formulations for the treatment of cystic fibrosis.

Cystic fibrosis (CF), a fatal genetic condition, causes thick, sticky mucus. It also causes pancreatic dysfunction, bacterial infection, and increased salt loss. Currently available treatments can improve the patient's quality of life. Drug delivery aided by nanotechnology has been explored to alter the pharmacokinetics and toxicity of drugs. In this short review, we aim to summarize various conventional formulations and highlight advanced formulations delivered via the pulmonary route for the treatment of CF. There is considerable interest in advanced drug delivery formulations addressing the various challenges posed by CF. Despite their potential to be translated for clinical use, we anticipate that a significant amount of effort may still be required for translation to the clinic.

Nano Drug Delivery Strategies for an Oral Bioenhanced Quercetin Formulation.

Quercetin, a naturally occurring flavonoid, has been credited with a wide spectrum of therapeutic properties. However, the oral use of quercetin is limited due to its poor water solubility, low bioavailability, rapid metabolism, and rapid plasma clearance. Quercetin has been studied extensively when used with various nanodelivery systems for enhancing quercetin bioavailability. To enhance its oral bioavailability and efficacy, various quercetin-loaded nanosystems such as nanosuspensions, polymer nanoparticles, metal nanoparticles, emulsions, liposomes or phytosomes, micelles, solid lipid nanoparticles, and other lipid-based nanoparticles have been investigated in in-vitro cells, in-vivo animal models, and humans. Among the aforementioned nanosystems, quercetin phytosomes are attracting more interest and are available on the market. The present review covers insights into the possibilities of harnessing quercetin for several therapeutic applications and a special focus on anticancer applications and the clinical benefits of nanoquercetin formulations.

Biofabrication of nanoparticles: sources, synthesis, and biomedical applications.

Nanotechnology is an emerging applied science delivering crucial human interventions. Biogenic nanoparticles produced from natural sources have received attraction in recent times due to their positive attributes in both health and the environment. It is possible to produce nanoparticles using various microorganisms, plants, and marine sources. The bioreduction mechanism is generally employed for intra/extracellular synthesis of biogenic nanoparticles. Various biogenic sources have tremendous bioreduction potential, and capping agents impart stability. The obtained nanoparticles are typically characterized by conventional physical and chemical analysis techniques. Various process parameters, such as sources, ions, and temperature incubation periods, affect the production process. Unit operations such as filtration, purification, and drying play a role in the scale-up setup. Biogenic nanoparticles have extensive biomedical and healthcare applications. In this review, we summarized various sources, synthetic processes, and biomedical applications of metal nanoparticles produced by biogenic synthesis. We highlighted some of the patented inventions and their applications. The applications range from drug delivery to biosensing in various therapeutics and diagnostics. Although biogenic nanoparticles appear to be superior to their counterparts, the molecular mechanism degradation pathways, kinetics, and biodistribution are often missing in the published literature, and scientists should focus more on these aspects to move them from the bench side to clinics.

Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations.

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia.

Development of Biocompatible Ciprofloxacin-Gold Nanoparticle Coated Sutures for Surgical Site Infections.

Surgical site infections (SSIs) are mainly observed after surgeries that use biomaterials. The aim of this present work was to develop ciprofloxacin hydrochloride (CPH)-loaded gold nanoparticles. These ciprofloxacin-gold nanoparticles were coated onto a sterile surgical suture using an adsorption technique, followed by rigidization via ionotropic crosslinking using sodium alginate. Furthermore, UV-visible spectroscopy, infrared spectroscopy, and scanning electron microscopy were used to characterize the samples. The particle size of the nanoparticles was 126.2 ± 13.35 nm with a polydispersity index of 0.134 ± 0.03, indicating nanosize formation with a monodispersed system. As per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, stability studies were performed for 30 days under the following conditions: 2-8 °C, 25 ± 2 °C/60 ± 5% RH, and 40 ± 2 °C/75 ± 5% RH. For both Gram-negative and Gram-positive bacteria, the drug-coupled nanoparticle-laden sutures showed a twofold higher zone of inhibition compared with plain drug-coated sutures. In vitro drug release studies showed a prolonged release of up to 180 h. Hemolysis and histopathology studies displayed these sutures' acceptable biocompatibility with the healing of tissue in Albino Swiss mice. The results depict that the use of antibiotic-coated sutures for preventing surgical site infection for a long duration could be a viable clinical option.

Structural Elucidation of Alkali Degradation Impurities of Favipiravir from the Oral Suspension: UPLC-TQ-ESI-MS/MS and NMR.

A novel stability-indicating, reversed-phase, high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of favipiravir in an oral suspension. The effective separation of favipiravir and its degradation products was achieved on a Zorbax Eclipse Plus C18 column (5 µm particle size, 150 mm length × 4.6 mm diameter). The mobile phase was prepared by mixing 5 mM of phosphate buffer (pH 3.5) and methanol in a 75:25 v/v ratio delivered at a 1.0 mL/min flow rate. The eluents were monitored using a photodiode array detector at a wavelength of 322 nm. The stability-indicating nature of this method was evaluated by performing force degradation studies under various stress conditions, such as acidic, alkali, oxidative, thermal, and photolytic degradation. Significant degradation was observed during the alkali stress degradation condition. The degradation products generated during various stress conditions were well separated from the favipiravir peak. In addition, the major degradation product formed under alkali stress conditions was identified using UPLC-ESI-TQ-MS/MS and NMR. Method validation was performed according to the ICH Q2 (R1) guideline requirements. The developed method is simple, accurate, robust, and reliable for routine quality control analysis of favipiravir oral suspensions.

Fast-Fed Variability: Insights into Drug Delivery, Molecular Manifestations, and Regulatory Aspects.

Among various drug administration routes, oral drug delivery is preferred and is considered patient-friendly; hence, most of the marketed drugs are available as conventional tablets or capsules. In such cases, the administration of drugs with or without food has tremendous importance on the bioavailability of the drugs. The presence of food may increase (positive effect) or decrease (negative effect) the bioavailability of the drug. Such a positive or negative effect is undesirable since it makes dosage estimation difficult in several diseases. This may lead to an increased propensity for adverse effects of drugs when a positive food effect is perceived. However, a negative food effect may lead to therapeutic insufficiency for patients suffering from life-threatening disorders. This review emphasizes the causes of food effects, formulation strategies to overcome the fast-fed variability, and the regulatory aspects of drugs with food effects, which may open new avenues for researchers to design products that may help to eliminate fast-fed variability.

Polymeric Micelles for Breast Cancer Therapy: Recent Updates, Clinical Translation and Regulatory Considerations.

With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.

Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles.

Solid lipid nanoparticles (SLNs) are an alternate carrier system to liposomes, polymeric nanoparticles, and inorganic carriers. SLNs have attracted increasing attention in recent years for delivering drugs, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics. These nanocarriers have attracted industrial attention due to their ease of preparation, physicochemical stability, and scalability. These characteristics make SLNs attractive for manufacture on a large scale. Currently, several products with SLNs are in clinical trials, and there is a high possibility that SLN carriers will quickly increase their presence in the market. A large-scale manufacturing unit is required for commercial applications to prepare enough formulations for clinical studies. Furthermore, continuous processing is becoming more popular in the pharmaceutical sector to reduce product batch-to-batch differences. This review paper discusses some conventional methods and the rationale for large-scale production. It further covers recent progress in scale-up methods for the synthesis of SLNs, including high-pressure homogenization (HPH), hot melt extrusion coupled with HPH, microchannels, nanoprecipitation using static mixers, and microemulsion-based methods. These scale-up technologies enable the possibility of commercialization of SLNs. Furthermore, ongoing studies indicate that these technologies will eventually reach the pharmaceutical market.

Pharmacokinetics and Anti-Diabetic Studies of Gliclazide Nanosuspension.

Gliclazide (GCZ), an antidiabetic medication, has poor solubility and limited oral bioavailability due to substantial first-pass metabolism. Thus, the purpose of the current study was to optimize and formulate a GCZ nanosuspension (NS) employing the antisolvent precipitation technique. A three-factor, three-level Box-Behnken design (BBD) was used to examine the impact of the primary formulation factors (drug concentration, stabilizer, and surfactant %) on particle size. The optimized NS contains 29.6 mg/mL drug, 0.739% lecithin, and 0.216% sodium dodecyl sulfate (SDS). Under scanning microscopy, the topography of NS revealed spherical particles. Furthermore, NS had a much better saturation solubility than the pure material, which resulted in a rapid dissolving rate, which was attributed to the amorphous structure and smaller particle size of the NS particles. Studies on intestinal permeability using the in vitro noneverted intestinal sac gut method (duodenum, jejunum, and ileum) and single-pass intestinal permeability (SPIP) techniques showed that the effective permeability was also increased by more than 3 fold. In the pharmacokinetic study, the Cmax and AUC0-t values of NS were approximately 3.35- and 1.9-fold higher than those of the raw medication and marketed formulation (MF). When compared to plain drug and commercial formulations, the antidiabetic efficacy of NS demonstrated that it had a significant impact on lowering glucose levels.

Therapeutic Potential of Naringenin Nanosuspension: In Vitro and In Vivo Anti-Osteoporotic Studies.

Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.

Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics.

The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w/w of Smix (Labrasol and Transcutol HP, and 40% w/w of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC0-t24 (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.

Novel and investigational therapies for wet and dry age-related macular degeneration.

Age-related macular degeneration (AMD) is a macular degenerative eye disease, the major cause of irreversible loss of central vision. In this review, we highlight current progress and future perspectives of novel and investigational therapeutic strategies in the drug pipeline, including anti-vascular endothelial growth factor (VEGF) agents, bispecific antibodies, biosimilars, small molecules, gene therapy, and long-acting drug delivery strategies for both dry and wet AMD. We anticipate that biologics with dual functionalities and combined therapies with long-acting capabilities will lead the wet AMD pipeline. Sustained-release platforms also show potential. However, significant breakthroughs are yet to be made for dry AMD. The personalized approach might be well suited in the scenario of diverse genetic variations in both conditions.

An overview of oral insulin delivery strategies (OIDS).

Despite tremendous efforts, the world continues its fight against the common chronic disease-diabetes. Diabetes is caused by elevated glucose levels in the blood, which can lead to several complications like glaucoma, cataract, kidney failure, diabetic ketoacidosis, heart attack, and stroke. According to recent statistics, China, India, and the US rank at the top three positions with regards to the number of patients affected by diabetes. Ever since its discovery, insulin is one of the major therapeutic molecules that is used to control the disease in the diabetic population, worldwide. The most common route of insulin administration has been the subcutaneous route. However, the limitations associated with this route have motivated global efforts to explore alternative strategies to deliver insulin, including pulmonary, transdermal, nasal, rectal, buccal, and oral routes. Oral insulin delivery is the most convenient and patient-centered route. However, the oral route is also associated with numerous drawbacks that present significant challenges to the scientific fraternity. The human physiological system acts as a formidable barrier to insulin, limiting its bioavailability. The present review covers the major barriers against oral insulin delivery and explains formulation strategies that have been adopted to overcome these barriers. The review focuses on oral insulin delivery strategies (OIDS) for increasing the bioavailability of oral insulin, including nanoparticles, microparticles, nano-in-microparticles, hydrogels, tablets, capsules, intestinal patches, and use of ionic liquids. It also highlights some of the notable recent advancements and clinical trials in oral insulin delivery. This formulation based OIDS may significantly improve patient compliance in the treatment of diabetes.

Bionanofactories for Green Synthesis of Silver Nanoparticles: Toward Antimicrobial Applications.

Among the various types of nanoparticles and their strategy for synthesis, the green synthesis of silver nanoparticles has gained much attention in the biomedical, cellular imaging, cosmetics, drug delivery, food, and agrochemical industries due to their unique physicochemical and biological properties. The green synthesis strategies incorporate the use of plant extracts, living organisms, or biomolecules as bioreducing and biocapping agents, also known as bionanofactories for the synthesis of nanoparticles. The use of green chemistry is ecofriendly, biocompatible, nontoxic, and cost-effective. We shed light on the recent advances in green synthesis and physicochemical properties of green silver nanoparticles by considering the outcomes from recent studies applying SEM, TEM, AFM, UV/Vis spectrophotometry, FTIR, and XRD techniques. Furthermore, we cover the antibacterial, antifungal, and antiparasitic activities of silver nanoparticles.